Patients receiving the anti-CD38 monoclonal antibody isatuximab in addition to the standard three- component induction therapy lenalidomide, bortezomib, and dexamethasone (RVd) for newly diagnosed multiple myeloma were significantly more likely to achieve minimal residual disease negativity (no evidence of cancer in the bone marrow) compared with those receiving RVd alone, according to results from the first primary endpoint of a phase III trial.
About half (50.1%) of study participants who received isatuximab-RVd versus 35.6% of those receiving RVd only achieved minimal residual disease negativity in the bone marrow after their induction treatment.
“This is the first phase III trial to successfully challenge a standard of care that is broadly used in the U.S. and Europe,” said Prof. Hartmut Goldschmidt, MD, of the Heidelberg University Hospital (UKHD) and National Center of Tumor Diseases Heidelberg (NCT) in Germany. “Our results support this treatment as a new standard of care in transplant-eligible patients with newly diagnosed myeloma.”
Treatment for multiple myeloma, a cancer of the plasma cells that is most common in people over the age of 60, has advanced substantially in recent years, achieving a 10-year survival rate of up to 70%.
By adding isatuximab to RVd, the researchers aimed to further increase survival rates and completely eradicate the cancer in the bone marrow for more patients.
Isatuximab is approved in the U.S., Europe, and other countries for multiple myeloma patients who have already undergone previous rounds of treatment.
This new trial assessed its use as part of the first-line treatment for newly diagnosed, transplant-eligible patients up to 70 years of age.
“Isatuximab acts in two ways – one is the direct effect of the antibody on myeloma cells, and the other is the immunostimulatory effect,” said Dr. Goldschmidt. “The idea is that if the immune system is stimulated by isatuximab, treatment of myeloma will be more effective.”
The trial enrolled 662 newly diagnosed patients at 67 medical centers throughout Germany. Half received induction therapy isatuximab plus RVd and half received RVd alone.
The duration of induction therapy was 18 weeks for both treatment arms. In addition to meeting the trial’s primary endpoint for minimal residual disease negativity in the bone marrow, those receiving isatuximab were significantly more likely to achieve a complete response or a very good partial response and less likely to show evidence of disease progression.
The researchers also found no differences among subgroups, suggesting all patients benefit from the addition of isatuximab to RVd.
There was no major difference between groups in terms of overall adverse events or serious adverse events.
The most common adverse events in both groups were blood and lymphatic system disorders, infections, and nervous system disorders, with low white blood cell counts being more frequent in the isatuximab-RVd group.
The trial is continuing and will next assess the impact of isatuximab-RVd versus RVd induction therapy after autologous stem cell transplantation, as well as the drug’s potential effects when used as part of the maintenance regimen with lenalidomide.